Studies were directed toward determining the steps involved in the differentiation of B cells into immunoglobulin synthesizing and secreting plasma cells. Special emphasis was laid on developing new techniques to study the role of helper T cells, macrophages, and suppressor cells in these immune regulatory processes and to define defects in these immunoregulatory cell interactions in patients with immune dysfunctions. Recombinant DNA technology has been applied to study the arrangement and rearrangement of immunoglobulin genes in lymphocytic leukemias and lymphocyte cell lines. Leukemias of both suppressor and helper T cells have been identified. Excessive numbers of suppressor T cells have been demonstrated in association with agammaglobulinemia, selective IgA deficiency, suppressor leukemias, infectious mononucleosis, and post-transplantation immunodeficiency state. In studies of leukemias and cell lines, it was shown that human B-cells rearrange their expressed allele and may retain, rearrange, or delete the non-expressed allele. Unexpectedly the kappa gene was deleted in lambda expressing B cells.